JPS6016906A - External drug for skin - Google Patents

Abstract

PURPOSE:To provide an external drug for skin, having high stability in the substrate and effective for the prevention and remedy of melanosis, by compounding a substrate for external use with arbutin as a hydroquinone-producing raw material. CONSTITUTION:The objective drug can be prepared by using arbutin of formula (4-hydroxyphenyl-beta-D-glucopyranoside) as an active component. The amount of arbutin is preferably 0.1-5wt% based on the whole composition. The drug can be applied effectively for the prevention and remedy of melanosis by the action of hydroquinone. Arbutin has by far higher stability than hydroquinone, and nevertheless, is decomposed into hydroquinone and glucose rapidly in the presence of the hydrolase in the skin and exhibits the remedying effect to melanosis. It can be used in the form of ointment, cream, milky lotion, lotion, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an external skin preparation effective for the prevention and treatment of skin pigmentation disorders through the action of hydroquinone. More specifically, arbutin (4-
The present invention relates to an external preparation containing hydroxyphenyl-β-D glucopyranoid (hydroxyphenyl-β-D glucopyranoid) in a skin external preparation.

It has been well known that no-hydroquinone is a therapeutic agent for skin pigmentation and is effective in whitening the skin and treating age spots, freckles, melasma, and the like.

However, the above-mentioned nohedroquinone is extremely unstable to heat and air, and is particularly susceptible to decomposition, discoloration, and other deterioration due to heat, air, etc. in external skin base materials containing moisture. For this reason, many studies have been conducted to stabilize hydroquinone, but no effective stabilization method that is practically satisfactory for external skin preparations has been found so far.

The present inventor has conducted various studies to obtain an external preparation that stably supplies hydroquinone to the skin, which eliminates the above-mentioned drawbacks of conventional skin pigmentation treatment agents. The inventors have completed the present invention by discovering that the stability of the antidepressant in the skin is high, and as a result, good results can be obtained in the prevention and treatment of skin deposits.

Arbutin applied to the present invention has the structure shown below and does not significantly inhibit melanin production by itself, but the present inventor has discovered that it exists much more stably than hydroquinone in external skin preparations. It was confirmed that in the presence of hydrolytic enzymes in the skin, it was very easily converted into no-hydroquinone and glucose, as shown in the following formula, and showed an effect of improving pigmentation.

Arbutin Glucose Hydroquino/i.e. 1According to the findings of the present invention, hydroquinone and arbutin at 25°C
Table 1 shows a comparison of the decomposition rates of each H aqueous solution (10 molar concentration: Matsu Kuilpen I, 05 H).

In the case of pi-I 5, 4, the half-life of hydroquinone is 2
Arbutin shows a remarkable stability of 124 days, compared to 124 days.8 It was proven in an experiment using guinea pig skin homogenate that arbutin produces 7-hydroquinone in the skin3. A 0.4-thick piece of guinea pig skin was collected using a Castroviejo ceratome. 0.1 mol citric acid, phosphate buffer (PH7.0) per 1 gram of collected skin
4.04 was added and homogenized using a glass homogenizer to obtain a nate solution.

Arbutin is 0.1M citric acid, phosphate buffer (P)
(,7,0) was dissolved in water at a concentration of 7% by weight (hereinafter referred to as wt%
(represented by a division).

Mix 2.5 ml of guinea pig skin homogenate and 1% Arbutin's liquid at 37°C at 0.5, 1, 2.

The reaction was allowed to proceed for 4 hours. After the reaction is complete, centrifuge the whole reaction solution (3
, 50 rpm, 10 minutes) Tetrahydrofuran was added to the obtained supernatant liquid to make it exactly 50 d.

A 5 μt aliquot was placed on the tetrahydrofuran solution, and the hydroquinone produced was quantified by high performance liquid chromatography.

The results are shown in Ripa 5I. As shown in the figure, hydroquinone was clearly produced by the arbutinha skin homogenate.

In the present invention, arbutin is used in a skin external preparation at a ratio of 0.1 to 5% by weight. Among these.

When used in external preparations such as cosmetics whose sole purpose is to prevent dark spots and freckles caused by sunburn, the amount is 0.1% by weight or more, and when used in external preparations as a drug for the treatment of pigmentation disorders. In this case, a layer of 1 weight or more can be used as an effective layer. If the amount used is less than 1 part, the purpose of the present invention may not be achieved, and if it exceeds 5%, it may be undesirable from the point of view of safety for the skin.

The base material for external use on the skin used in the present invention may be any of those conventionally used in this type of external preparation for the skin, and includes, for example, those in the form of ointments, creams, milky lotions, and lotions. Here, for example, beeswax is used as the base material for ointment.
Squalane, KD-Wax 123. Liquid fluorine, sorbitan monooleate, and provilparabennato can be used. Cream base materials that can be used include petrolatum, cetanol, stearyl alcohol rough-in, and cetomacrogol-1000° methyl paraben.Furthermore, lotion base materials include ethanol, polyoxyethylene-added castor oil, and methyl paraben.

Examples include propylene glycol.

Using these raw materials as appropriate, external skin preparations in appropriate forms such as ointments, cream lotions, and milky lotions are prepared by conventional methods.

Here, the pigmentation improving effect of the external preparation of the present invention will be shown.

Cream of the present invention containing 2% arbutin (A) and base without arbutin, that is, control cream [B] 7a
- A clinical test was conducted to determine the curative effect of continuous use for 3 months on 15 women with melasma who were fermentally equivalent. Results table 2
As shown in Figure 2, IJ-mu [A] was clearly more effective in improving melasma than the control cream [B].

Table 2 The external preparation of the present invention has the above-mentioned structure, and thereby has the following effects 1N.

(1) Arbutin can be incorporated extremely stably into a base material for external use on the skin. Moreover, since arbutin easily generates all of the hydroquinone when applied to the skin, the external preparation of the present invention can effectively supply the effective amount of hydroquinone to the skin.

(2) As a result, the external preparation of the present invention has an extremely high pigmentation improving effect.

(3) Furthermore, the external preparation of the present invention itself is a safe external preparation that does not have toxic irritation, bad odor, side effects, etc.

Examples are shown below to further illustrate the present invention.

Example 1 (Cream) A mixture of 15.0% petrolatum, 4.5% cetanol, 4.3% stearyl alcohol, 3.0% liquid paraffin and 10002.0% cetomacrogol was melted by heating to 70°C. , plus 0.2% methylparaben, 2.0% arbutin, 1 tsp fragrance and 68.9% purified water.
A mixture heated to 70° C. was added, uniformly emulsified, and then cooled to obtain a cream product.

Example 2 (Lotion) A mixture of ethanol 10.0φ, polyoxyethylene (50) hydrogenated castor oil 0.5%, methylparaben 0.1% and fragrance 0.1%, and propylene glycol 5
．． 0%, arbutin 0.8% and purified water 83.5
% mixture was mixed at room temperature to obtain a lotion product.

Example 3 (Oint) Beeswax 2.5%, squalane 7.5%, KD-wax 123. 7.5%, liquid paraffin 10.0t, petrolatum 22.5%, sorbitan monooleate 3
．． A mixture of 5%, POE sorbitan monooleate 1.5% and Amerchol XL-1011, 0% was melted thermothermally and maintained at a temperature above 70°C, to which Alfti:i 3.0% + Provirino was added. Pen 0.
A mixture of 1% and 40.9% purified water heated to 70°C or above was added, stirred, and then cooled to obtain an ointment product.

[Brief explanation of the drawing]

The figure is a graph showing the effect of hydroquinone production from arbutin when the homogenate is used on guinea pig skin. Reaction time (hours)

Claims (2)

[Claims] (1) External skin shavings characterized by containing arbutin in the base material for external use on the skin (2) The skin external preparation according to claim 1, characterized in that the blending ratio of arbutin is 0.1 to 5% by weight of the whole;